Antibiotics are one of the most important and widely used medicines. Their extensive use has led to the resistance development by their pathogenic bacterial targets. The emergence of multi-drug resistant bacteria has become a global public health threat. Serious infection of multi-drug resistant microorganisms often causes considerable patient mortality and modality. For example, more people died from methicillin-resistant Staphylococci aureus (MRSA) infection than those from HIV/AIDS, Parkinson's disease and homicide combined. The development of structural analogs of existing antibiotics had kept up with the emergence of new resistance until 20 years ago. Currently, there are not enough analogs in the antibiotic pipeline to combat imminent and future resistance emergence. In addition, the search for new structural classes of antibiotics has yielded only two new classes of antibacterials since 1960. The Pharmaceutical industry has devoted significant resources to high-throughput screening of large compound libraries against targets identified from genetic methods in recent years. However, these efforts have made limited progress.
Resistance-modifying agents (RMAs) are a highly favorable alternative. These target non-essential resistance conferring genes and can further expand the life span of antibiotics that are currently used in the clinics, which have already been optimized for toxicity and large-scale production. For example, clavulanic acid is a β-lactamase inhibitor. Its use in combination with amoxicillin restores the efficacy of amoxicillin against many β-lactamase producing bacteria.
Despite current efforts in identification and synthesis of RMAs, there is a continuing and urgent need for RMAs that can extend the usefulness of antibiotics for the treatment of drug resistant bacteria.